We seek to understand the circuitry of visual cortex, the rules underlying its activity-dependent development, and the computational functions these subserve. These understandings are critical to our understanding both of normal vision and of its central disorders including amblyopia and strabismus. We focus on V1 as a model system. We use modeling to test coherent hypotheses as to the circuitry underlying V1 functional response properties and the plasticity rules underlying circuit development. Modeling allows testing of an integrated picture of circuit structure and/or developmental rules against a variety of experimental results and the development of new and unanticipated tests of that picture. The specific aims of this project are: (1) To create biologically identifiable and testable models of the mature circuitry of visual cortex. In particular, we will test the hypotheses (i) That intracellular as well as extracellular classical RF responses in LGN-recipient V1 simple cells, including a contrast-dependent decrease in voltage noise that is critical to contrast-invariant orientation tuning, can be quantitatively understood from simple, essentially feedforward models. (ii) That the apparent determination of the response tuning properties of LGN-recipient V1 simple cells by their feedforward input and the strong recurrence seen in V1 can be integrated into a coherent circuit model of layers 2/3 and 4 under the hypothesis, for which we provide evidence, that the recurrence functions as an inhibition-stabilized network: a network in which excitatory recurrence alone is strong enough to cause instability, but the circuit is stabilized by feedback inhibition. We will determine the conditions under which this circuit can account for classical and extra-classical receptive field properties and the structure observed in spontaneous activity, clearly isolate the contribution of the recurrence to responses, and develop novel tests of this architecture. (2) To create biologically identifiable and testable models of the development of the circuitry of visual cortex. In particular, studying the critical period (CP) for monocular deprivation in mouse V1, we will develop a unified model of homeostatic and Hebbian CP plasticity, and theoretically test the hypothesis that the induction of the CP by maturation of inhibition occurs due to an increase in the ratio of visual activity to spontaneous activity caused by that maturation. PUBLIC HEALTH RELEVANCE The visual cortex is the brain structure with which we see, creating our visual perception from the information provided by the eyes. To understand both how we see normally and how central visual disorders such as strabismus and amblyopia arise and can be treated, it is critical to understand how the circuitry of visual cortex processes visual information and is organized by visual experience. These are our research aims.